What is the recommended treatment plan for patients with hypercholesterolemia (high cholesterol) using Repatha (evolocumab)?

Repatha (Evolocumab) Treatment Plan for Hypercholesterolemia

Repatha (evolocumab) should be administered at 140 mg subcutaneously every 2 weeks OR 420 mg once monthly as an adjunct to maximally tolerated statin therapy in adults with established cardiovascular disease or primary hyperlipidemia who require additional LDL-C lowering. 1, 2

FDA-Approved Indications

Evolocumab is approved for the following specific populations 1, 2:

• Adults with established cardiovascular disease to reduce risk of MI, stroke, and coronary revascularization
• Adults with primary hyperlipidemia (including heterozygous familial hypercholesterolemia) as adjunct to diet, alone or with other lipid-lowering therapies
• Pediatric patients aged ≥10 years with heterozygous familial hypercholesterolemia to reduce LDL-C
• Adults and pediatric patients aged ≥10 years with homozygous familial hypercholesterolemia as adjunct to other LDL-C-lowering therapies

Dosing Regimens by Clinical Scenario

Adults with ASCVD or Primary Hyperlipidemia

Standard dosing: 140 mg subcutaneously every 2 weeks OR 420 mg once monthly 1, 2

• Administer in the abdomen, thigh, or upper arm, rotating injection sites 1, 2
• When switching between regimens, give the first dose of the new regimen on the next scheduled date of the prior regimen 2

Homozygous Familial Hypercholesterolemia

Initial dose: 420 mg once monthly subcutaneously 1, 2

• If clinically meaningful response not achieved after 12 weeks, increase to 420 mg every 2 weeks 1, 2
• For patients on LDL apheresis, may initiate 420 mg every 2 weeks to correspond with apheresis schedule; administer after apheresis is complete 1, 2

Administration of 420 mg Dose

Use either the prefilled single-dose on-body infuser (Pushtronex system) OR give 3 consecutive 140 mg injections within 30 minutes at different injection sites 1, 2

Clinical Decision Algorithm for Initiating Repatha

Step 1: Optimize Background Therapy

Before considering Repatha, ensure the patient is on maximally tolerated statin therapy 1

• Check adherence first and reinforce importance of compliance 1
• If adherence is satisfactory, add ezetimibe per local guidance 1
• Reassess LDL-C after 4 weeks of ezetimibe 1

Step 2: Apply LDL-C Thresholds

For patients with established ASCVD: Consider Repatha if LDL-C remains elevated despite maximally tolerated statin plus ezetimibe 1

For familial hypercholesterolemia without clinical ASCVD 1:

• LDL-C >180 mg/dL (>4.5 mmol/L): Consider PCSK9 inhibitor
• LDL-C >140 mg/dL (>3.6 mmol/L) with additional risk factors: Consider PCSK9 inhibitor

Additional risk severity indices that lower the threshold 1:

• Diabetes with target organ damage or major risk factors
• Lipoprotein(a) >50 mg/dL
• Smoking or marked hypertension (≥160/100 mmHg)
• Age ≥40 years without treatment
• Premature ASCVD in first-degree relatives (<55 years males, <60 years females)

Step 3: Monitor Response

Assess LDL-C as early as 4 weeks after initiation 1, 2

• The LDL-lowering effect can be measured at this timepoint 2
• Continue monitoring at clinically appropriate intervals 2

Expected Efficacy

LDL-C reduction: 59-64% when added to maximally tolerated statin therapy, achieving median LDL-C levels as low as 30 mg/dL 1, 3

Additional lipid effects 3:

• 27% reduction in lipoprotein(a)
• 51% reduction in non-HDL-C
• 16% reduction in triglycerides

Cardiovascular outcomes: In the FOURIER trial with 27,564 patients with prior ASCVD, evolocumab reduced 3:

• Composite endpoint (CV death, MI, stroke, revascularization, or hospitalization for unstable angina) by 15% (11.3% vs. 9.8%; P <0.001)
• Combined endpoint of CV death, MI, or stroke by 20% (7.4% vs. 5.9%; P <0.001)

Safety Profile and Contraindications

Contraindication: History of serious hypersensitivity reaction to evolocumab or any excipients 1, 2

Common adverse effects (>5%) 1, 2:

• Nasopharyngitis
• Upper respiratory tract infection
• Influenza
• Back pain
• Injection site reactions
• Diabetes mellitus (in patients with established CVD)

Important safety consideration: Angioedema has occurred; if signs or symptoms of serious hypersensitivity reactions occur, discontinue treatment, treat according to standard of care, and monitor until signs and symptoms resolve 1, 2

Very low LDL-C levels: Evidence suggests no detrimental impact on steroid hormone production, enterohepatic circulation of bile acids, or neuronal cell function, even with LDL-C levels <20 mg/dL 1

Critical Prescribing Considerations

Latex sensitivity: Repatha is available in presentations that either contain dry natural rubber (latex derivative) in the needle cover or are latex-free; prescribe the latex-free presentation for latex-sensitive individuals 2

Drug interactions: No clinically significant drug-drug interactions identified 1

Pregnancy/lactation: Safety data in humans are limited; use clinical judgment 1

Cost and access: Prior authorization is typically required; this can be a burdensome process 1

Homozygous FH with negative/negative LDLR mutations: Treatment not recommended in patients with LDL receptor activity below 2%, as some level of LDL receptor activity is required for efficacy 1